Early-stage Non-small Cell Lung Cancer Research Articles

P1.25-15 Trends and Disparities in Curative-Intent Treatment for Early-Stage Non-Small Cell Lung Cancer: A Population-Based Analysis of Surgery and SBRT

P1.25-15 Trends and Disparities in Curative-Intent Treatment for Early-Stage Non-Small Cell Lung Cancer: A Population-Based Analysis of Surgery and SBRT

EP07.05-09 Oncologic Outcomes of Stereotactic Body Radiotherapy in Early-Stage Non-Small Cell Lung Cancer Patients with Interstitial Lung Disease

EP07.05-09 Oncologic Outcomes of Stereotactic Body Radiotherapy in Early-Stage Non-Small Cell Lung Cancer Patients with Interstitial Lung Disease

EP07.02-14 Image-Guided Thermal Ablation of Early-Stage Non-small Cell Lung Cancer; Five-Year Outcome

EP07.02-14 Image-Guided Thermal Ablation of Early-Stage Non-small Cell Lung Cancer; Five-Year Outcome

EP07.01-16 The Relationship of FDG PET-SUVm and Glucose Metabolism and Contribution to Early-Stage Non-Small Cell Lung Cancer Survival

EP07.01-16 The Relationship of FDG PET-SUVm and Glucose Metabolism and Contribution to Early-Stage Non-Small Cell Lung Cancer Survival

EP07.01-11 Ablation of Early-Stage Non-Small Cell Lung Cancer in Patients With Interstitial Lung Disease: A Multicenter Retrospective Cohort Study

EP07.01-11 Ablation of Early-Stage Non-Small Cell Lung Cancer in Patients With Interstitial Lung Disease: A Multicenter Retrospective Cohort Study

EP07.03-14 Effect of Lymph Node Dissection on Recurrence and Survival Following Thoracoscopic Segmentectomy for Early-Stage Non-small Cell Lung Cancer

EP07.03-14 Effect of Lymph Node Dissection on Recurrence and Survival Following Thoracoscopic Segmentectomy for Early-Stage Non-small Cell Lung Cancer

P1.24-06 Prognostic Value of DNA Ploidy and Nucleotyping in Early-stage Non-small Cell Lung Cancer

P1.24-06 Prognostic Value of DNA Ploidy and Nucleotyping in Early-stage Non-small Cell Lung Cancer

EP01.01-14 Gender Differences in Clinical Course and Patient-Reported Outcomes among Patient with Early-Stage Non-Small Cell Lung Cancer

EP01.01-14 Gender Differences in Clinical Course and Patient-Reported Outcomes among Patient with Early-Stage Non-Small Cell Lung Cancer

OA12.04 Nivolumab After Stereotactic Ablative Radiotherapy for Early-Stage Non-Small Cell Lung Cancer: Randomized I-SABR Trial

OA12.04 Nivolumab After Stereotactic Ablative Radiotherapy for Early-Stage Non-Small Cell Lung Cancer: Randomized I-SABR Trial

Segmentectomy for patients with early-stage pure-solid non-small cell lung cancer.

For decades, lobectomy has been the recommended surgical procedure for non-small cell lung cancer (NSCLC), including for small-sized lesions. However, two recent pivotal clinical trials conducted by the Japanese Clinical Oncology Group/West Japan Oncology Group (JCOG0802/WJOG4607L) and the Cancer and Leukemia Group B (CALGB140503), which compared the survival outcomes between lobectomy and sublobar resection (the JCOG0802/WJOG4607L included only segmentectomy, not wedge resection), demonstrated the efficacy of sublobar resection in patients with early-stage peripheral lung cancer measuring ≤ 2 cm. The JCOG0802/WJOG4607L demonstrated the superiority of segmentectomy over lobectomy with respect to overall survival, implying the survival benefit conferred by preservation of the lung parenchyma. Subsequently, the JCOG1211 also demonstrated the efficacy of segmentectomy, even for NSCLC, measuring up to 3 cm with the predominant ground-glass opacity phenotype. Segmentectomy has become the standard of care for early-stage NSCLC and its indications are expected to be further expanded to include solid lung cancers > 2 cm. However, local control is still a major concern for segmentectomy for higher-grade malignant tumors. Thus, the indications of segmentectomy, especially for patients with radiologically pure-solid NSCLC, remain controversial due to the aggressive nature of the malignancy. In this study, we reviewed previous studies and discussed the efficacy of segmentectomy for patients with such tumors.

Barriers to Timely Lung Cancer Care in Early Stage Non–Small Cell Lung Cancer and Impact on Patient Outcomes

BackgroundOptimal time to treatment for early-stage lung cancer is uncertain. We examined causes of delays in care for Veterans who presented with early-stage non–small cell lung cancer (NSCLC) and whether workup time was associated with increased upstaging or all-cause mortality. MethodsWe performed a retrospective analysis of Veterans referred to our facility with radiographic stage I or II NSCLC between January 2013 to December 2017, with follow-up through October 2021. Patient demographics, tumor characteristics, time intervals of care, and reasons for delays were collected. Guideline concordance (GC) was defined as treatment within 14 weeks of abnormal image. Multivariable analyses were performed to determine association between delays in care, survival, and upstaging. ResultsData from 203 Veterans were analyzed. Median time between abnormal imaging to treatment was 17.7 weeks (IQR 12.7-26.6). Only 33% of Veterans received GC care. Most common patient-related delays were: intercurrent hospitalization/comorbidity (23%), no-shows (16%) and inability to reach Veteran (17%). Most common system-related delay: lack of scheduling availability (25%). Delays associated with upstaging: transportation issues, request for coordination of appointments, and unforeseen appointment changes. Rates of upstaging did not differ between GC and discordant groups (P = .6). GC care was not an independent predictor of mortality. Post-hoc, treatment within 8 weeks was associated with lower rates of upstaging (P = .05). ConclusionAlthough GC care did not impact survival or upstaging for early-stage NSCLC, shorter timeframes may be beneficial. Modifiable delays in care exist which may be addressed at an institutional level to improve timeliness of care.

PD-1/PD-L1 Inhibitors plus Chemotherapy Versus Chemotherapy Alone for Resectable Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: The benefit of adding programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors to the treatment of early-stage non-small cell lung cancer (NSCLC), both neoadjuvant therapy (NAT) and adjuvant therapy (AT), is not yet fully elucidated. Methods: We searched PubMed, Embase, and Cochrane databases for randomized controlled trials (RCT) that investigated PD-1/PD-L1 inhibitors plus chemotherapy for resectable stage NSCLC. We computed hazard ratios (HRs) or odds ratios (ORs) for binary endpoints, with 95% confidence intervals (CIs). Results: A total of seven RCTs comprising 3915 patients with resectable stage NSCLC were randomized to chemotherapy with or without PD-1/PD-L1 inhibitors as NAT or AT. As NAT, the PD-1/PD-L1 inhibitors plus chemotherapy group demonstrated significantly improved overall survival (HR 0.66; 95% CI 0.51-0.86) and event-free survival (HR 0.53; 95% CI 0.43-0.67) compared with the chemotherapy alone group. There was a significant increase in favor of the PD-1/PD-L1 inhibitors plus chemotherapy group for major pathological response (OR 6.40; 95% CI 3.86-10.61) and pathological complete response (OR 8.82; 95% CI 4.51-17.26). Meanwhile, as AT, disease-free survival was significant in favor of the PD-1/PD-L1 inhibitors plus chemotherapy group (HR 0.78; 95% CI 0.69-0.90). Conclusions: In this comprehensive systematic review and meta-analysis of RCTs, the incorporation of PD-1/PD-L1 inhibitors alongside chemotherapy offers a promising prospect for reshaping the established treatment paradigms for patients diagnosed with resectable stages of NSCLC. Moreover, our analyses support that neoadjuvant administration with these agents should be encouraged, in light of the fact that it was associated with an increased survival and pathological response, at the expense of a manageable safety profile.

Systematic review and meta-analysis of immune checkpoint inhibitors as single agent or in combination with chemotherapy in early-stage non-small cell lung cancer: Impact of clinicopathological factors and indirect comparison between treatment strategies

BackgroundIn non-small cell lung cancer (NSCLC), the immune checkpoint inhibitors (ICI) revolution is rapidly moving from metastatic to early-stage, however, the impact of clinicopathological variables and optimal treatment sequencing remain unclear. MethodsRandomized controlled trials (RCTs) in patients with early-stage NSCLC treated with ICI as single agent or in combination with platinum-based chemotherapy (PCT) were included. Primary outcomes were pathological complete response (pCR), event free survival (EFS) (neoadjuvant/perioperative), and disease-free survival (DFS) (adjuvant). Secondary outcomes were major pathological response (MPR), overall survival (OS), toxicity, surgical outcomes (neoadjuvant/perioperative); OS and toxicity (adjuvant). An additional secondary endpoint was to compare EFS and OS between neoadjuvant and perioperative strategies. Results8 RCTs (2 neoadjuvant, 4 perioperative, 2 adjuvant) (4661 participants) were included. Neoadjuvant/perioperative ICI+PCT significantly improved pCR, EFS, OS, MPR and R0 resection compared to PCT. Adjuvant ICI significantly improved DFS compared to placebo. There was a significant subgroup interaction by PD-L1 status (χ2 = 10.72, P = 0.005), pCR (χ2 = 17.80, P < 0.0001), and stage (χ2 = 4.46, P = 0.003) for EFS. No difference according to PD-L1 status was found for pCR, with 14% of patients having PD-L1 negative tumors still experiencing a pCR. No interaction by PD-L1 status was found for DFS upon adjuvant ICI. Indirect comparison showed no difference in EFS and OS between neoadjuvant and perioperative ICI+PCT. ConclusionsPD-L1 status, pCR and stage impact on survival upon neoadjuvant/perioperative ICI. The restriction of neoadjuvant/perioperative ICI to PD-L1 + patients could preclude pCR and long-term benefit in the PD-L1- subgroup. Neoadjuvant and perioperative could be equivalent strategies.

Diagnostic Workup, Treatment Patterns, and Clinical Outcomes in Early-Stage IB-IIIA Non-Small-Cell Lung Cancer Patients in Denmark.

Despite recent improvements in early-stage non-small-cell lung cancer (NSCLC), disease relapse remains challenging. Moreover, real-world evidence on long-term follow-up of disease-free survival (DFS) and recurrence patterns in a large, unselected cohort of early-stage NSCLC patients is lacking. This cohort study aimed to assess clinical characteristics, diagnostic workup, treatment, survival, and risk of disease relapse among early-stage NSCLC patients. Adult patients with stage IB, II, or IIIA NSCLC diagnosed and/or treated at Aarhus University Hospital in Denmark from January 2010 to December 2020 were included and followed-up until May 2021. Comprehensive clinical data were collected from electronic medical records of eligible patients and linked to Danish register data. The study population comprised 1341 early-stage NSCLC patients: 22%, 40%, and 38% were diagnosed with stage IB, II, and IIIA disease, respectively. In total, 42% of patients were tested for epidermal growth factor receptor (EGFR), of whom 10% were EGFR-mutation-positive (EGFRm+). Half of all patients received surgery, and nine percent of patients received stereotactic body radiation therapy (SBRT). Disease-free survival 5 years post-diagnosis was 49%, 42%, and 22% for stage IB, II, and stage IIIA patients, respectively. DFS improved over time both for patients treated with surgery and SBRT. However, disease relapse remained a challenge, with approximately 40% of stage IIIA having relapsed 3 years post-diagnosis. This study contributes important knowledge that puts clinical trials on new perioperative treatment modalities for early-stage NSCLC patients into perspective. Our findings cover an essential evidence gap on real-world DFS and recurrence dynamics, confirming that despite an improvement in DFS over time and across different treatment modalities, disease relapse remains a monumental challenge. Therefore, better treatment strategies are needed.

The effect of platelet-to-lymphocyte ratıo (PLR) and glasgow prognostıc score (GPS) on recurrence, and survıval ın patıents undergoıng lobectomy for early-stage non-small cell lung cancer (NSCLC).

Tumor markers are indicators that can be used not only for cancer diagnosis but also for determining prognosis. Unfortunately, there is currently no tumor marker that reliably predicts the prognosis of lung cancer. In this study, we investigated the prognostic impact of the platelet-to-lymphocyte ratio (PLR) and Glasgow Prognostic Score (GPS), known as inflammation markers in peripheral blood, in patients who underwent resection for early-stage non-small cell lung cancer (NSCLC). We retrospectively analyzed the medical records of a total of 3300 patients who underwent surgery for NSCLC between 2010 and 2020. Among these patients, 250 met the inclusion criteria of lobectomy, pT1-T2N0 stage, and histology of adenocarcinoma or squamous cell carcinoma. Preoperative albumin, C-reactive protein (CRP), preoperative PLR, and postoperative 5th-day PLR values were determined from patient's peripheral blood data. The impact of these values on postoperative recurrence and survival was investigated. GPS was calculated based on preoperative CRP and albumin values, and patients were divided into 3 groups: 0 (mild), 1 (moderate), and 2 (severe). The relationship between preoperative GPS and survival was analysed. Among the included patients, 155 (62%) had adenocarcinoma and 95 (38%) had squamous cell carcinoma. A total of 185 (74%) patients had pT1 tumors, while 65 (26%) had pT2 tumors. During the postoperative follow-up period, local recurrence was observed in 28 (11.2%) patients and distant metastasis in 51 (20.4%) patients. The overall mortality rate was 19.6%. The 5-year survival rates for pT1 and pT2 tumors were 80.4% and 72.5%, respectively. Significant associations were found between preoperative PLR, postoperative PLR, and recurrence (p = 0.005 and p = 0.011). The expected overall survival (OS) was 103.4months in the mild GPS group, 91.8months in the moderate GPS group, and 50months in the severe GPS group. The relationship between GPS groups and OS was statistically significant (p = 0.005). Preoperative analysis of PLR and GPS may provide prognostic value in NSCLC patients who undergo surgical resection. Our study provides a rationale for further investigation of peripheral blood immune markers for prognostic purposes.

Hybrid delivery of cluster-set resistance training for individuals previously treated for lung cancer: the results of a single-arm feasibility trial

BackgroundIndividuals with non-small cell lung cancer (NSCLC) are burdened by long-lasting symptoms (e.g., dyspnea and fatigue) post-treatment. These symptoms often reduce physical activity levels and increase the risk of functional decline. Though we have previously proposed cluster-set resistance training to mitigate symptom burden in lung cancer, there is currently no data on the feasibility or acceptability of this mode of exercise in cancer. Therefore, the purpose of this study was to investigate the feasibility and acceptability of a hybrid-delivery home-based cluster-set resistance training program in individuals with NSCLC stages I–III (i.e., early stage).MethodsThis study aimed to recruit individuals with NSCLC stages I–III post-treatment to participate in 8 weeks of home-based resistance training, 3 days per week. The program included supervised sessions in the participants’ homes and virtual supervision via videoconferencing. The primary outcome measure of feasibility was evaluated through recruitment, retention, and intervention fidelity (i.e., proportion of exercise completed, relative to what was prescribed). Intervention acceptability (i.e., ease and quality of virtual delivery, level of difficulty, and home-based approach) was assessed using a 4-point Likert-type scale from “strongly disagree” to “strongly agree”.ResultsFourteen participants were recruited over a 6-month period, with 11 completing the intervention (2 withdrew due to unrelated illness, 1 withdrew due to requiring active treatment), yielding a retention rate of 79%. Characteristics of the participants who completed the intervention (n = 11) were as follows: mean age: 71 ± 10 years, mean BMI: 29.1 ± 6.5, and average time since diagnosis was 62 ± 51 months. Of completers, 27% were male, and 36% were Black; 10 were stage I (91%), and one was stage II (9%). Mean session attendance was 86.4 ± 9.5%. Mean intervention fidelity was 83.1 ± 13.1%. With regard to acceptability, > 90% of participants positively rated all aspects of the intervention delivery. No adverse events related to exercise were recorded.ConclusionsThe hybrid delivery of a home-based resistance exercise program for individuals previously treated for early-stage NSCLC was found to be safe and feasible. Adaptations to the program for future interventions are required, particularly surrounding resistance exercise programming, and intervention delivery with home visits.Trial registrationClinicalTrials.gov: NCT05014035. Registered January 20, 2021.

Stereotactic body radiation therapy in the treatment of early-stage non-small cell lung cancer.

Stereotactic body radiation therapy (SBRT) is now a standard treatment option for patients with early-stage non-small cell lung cancer (ES-NSCLC) who are unfit for surgery or refuse to undergo an operation. SBRT is a method of external beam radiotherapy that accurately delivers a high dose of irradiation in one or few treatment fractions. Intensive regimens of biologically effective dose ≥ 100 Gy are associated with good local control and overall survival, higher than in conventionally fractionated radiotherapy. There are still controversial areas in the SBRT indication where data are limited - indications for elderly and comorbid patients, indications for treatment without histological verification, treatment of central/ultracentral lesions, indications for tumors larger than 5 cm, indications for operable patients. The optimal follow-up practice of these patients also remains unclear, including the frequency of imaging, the use of PET-CT, and requirements for biopsy. CT changes after SBRT differ from those following conventional radiotherapy and it is difficult to distinguish them from tumor recurrence. Due to the high local control achieved with lung SBRT, data on the treatment of local failure are insufficient. The aim of the publication is to demonstrate the current information and the importance of SBRT for patients with ES-NSCLC.

Persistent racial disparities in refusal of resection in non-small cell lung cancer patients at high-volume and Black-serving institutions

BackgroundSurgical resection is the standard of care for early-stage non-small cell lung cancer. Black patients have higher surgical refusal rates than White patients. We evaluated factors associated with the refusal of resection and subsequent non-small cell lung cancer outcomes. MethodsWe identified patients with non-small cell lung cancer stages IA to IIIA eligible for surgical resection (lobectomy or pneumonectomy) listed between 2004 and 2017 in the National Cancer Database. We stratified hospitals by the proportion of Black patients served and lung cancer resection volume. We used multivariable regression models to identify factors associated with refusal of resection and assessed 5-year mortality using Kaplan–Meier analysis and Cox proportional hazard modeling. ResultsOf 221,396 patients identified, 7,753 (3.5%) refused surgery. Black race was associated with increased refusal (adjusted odds ratio 2.06, 95% confidence interval 1.90–2.22). Compared to White race, Black race was associated with increased refusal across the highest (adjusted odds ratio 2.29, 95% confidence interval 1.94–2.54), intermediate (adjusted odds ratio 2.05, 95% confidence interval 1.78–2.37), and lowest (adjusted odds ratio 1.77, 95% confidence interval 1.58–1.99) volume tertiles. Similarly, Black race was associated with increased refusal across the highest (adjusted odds ratio 1.97, 95% confidence interval 1.78–2.17), intermediate (adjusted odds ratio 2.08, 95% confidence interval 1.80–2.40), and lowest (adjusted odds ratio 1.53, 95% confidence interval 1.13–2.06) Black-serving tertiles. However, surgical resection yielded similar 5-year survival for Black and White patients. ConclusionRacial disparities in non-small cell lung cancer surgery refusal persist regardless of hospital volume or proportion of Black patients served. These findings suggest that a better understanding of patient and patient–provider level interventions could facilitate a better understanding of treatment decision-making.

Uniportal thoracoscopic extended right apical segmentectomy with virtual-assisted lung mapping: a case report

BackgroundPulmonary extended segmentectomy is an optional surgical treatment for early-stage non-small cell lung cancer that helps to achieve optimal surgical margins. Here, we describe a challenging instance of extended segmentectomy via uniportal video-assisted thoracic surgery with virtual-assisted lung mapping, a preoperative bronchoscopic dye marking procedure.Case presentationA 72-year-old woman presented with two tumors that were clinically diagnosed as early-stage lung cancer; extended right apical segmentectomy was indicated. Because the tumors had appeared unidentifiable intraoperatively, we performed virtual-assisted lung mapping for tumor localization and delineation of the optimal resection area. Surgery was conducted through a single port. All virtual-assisted lung mapping markings were visible. After dissection of the apical vessels and bronchi, a putative intersegmental line was determined using collateral ventilation. Based on the putative intersegmental plane identified by collateral ventilation and the virtual-assisted lung mapping markings, the resection line was delineated. Extended apical segmentectomy along the resection line was successfully performed via uniportal video-assisted thoracic surgery. The postoperative course was uneventful. The pathological diagnosis was minimally invasive adenocarcinoma and adenocarcinoma in situ.ConclusionsVirtual-assisted lung mapping can help to achieve optimal extended segmentectomy via uniportal video-assisted thoracic surgery.

Comparative analysis of dose calculation algorithms for CyberKnife-based stereotactic radiotherapy in lung cancer.

The accuracy of dose calculation is the prerequisite for CyberKnife (CK) to implement precise stereotactic body radiotherapy (SBRT). In this study, CK-MLC treatment planning for early-stage non-small cell lung cancer (NSCLC) were compared using finite-size pencil beam (FSPB) algorithm, FSPB with lateral scaling option (FSPB_LS) and Monte Carlo (MC) algorithms, respectively. We concentrated on the enhancement of accuracy with the FSPB_LS algorithm over the conventional FSPB algorithm and the dose consistency with the MC algorithm. In this study, 54 cases of NSCLC were subdivided into central lung cancer (CLC, n=26) and ultra-central lung cancer (UCLC, n=28). For each patient, we used the FSPB algorithm to generate a treatment plan. Then the dose was recalculated using FSPB_LS and MC dose algorithms based on the plans computed using the FSPB algorithm. The resultant plans were assessed by calculating the mean value of pertinent comparative parameters, including PTV prescription isodose, conformity index (CI), homogeneity index (HI), and dose-volume statistics of organs at risk (OARs). In this study, most dose parameters of PTV and OARs demonstrated a trend of MC > FSPB_LS > FSPB. The FSPB_LS algorithm aligns better with the dose parameters of the target compared to the MC algorithm, which is particularly evident in UCLC. However, the FSPB algorithm significantly underestimated the does of the target. Regarding the OARs in CLC, differences in dose parameters were observed between FSPB and FSPB_LS for V10 of the contralateral lung, as well as between FSPB and MC for mean dose (Dmean) of the contralateral lung and maximum dose (Dmax) of the aorta, exhibiting statistical differences. There were no statistically significant differences observed between FSPB_LS and MC for the OARs. However, the average dose deviation between FSPB_LS and MC algorithms for OARs ranged from 2.79% to 11.93%. No significant dose differences were observed among the three algorithms in UCLC. For CLC, the FSPB_LS algorithm exhibited good consistency with the MC algorithm in PTV and demonstrated a significant improvement in accuracy when compared to the traditional FSPB algorithm. However, the FSPB_LS algorithm and the MC algorithm showed a significant dose deviation in OARs of CLC. In the case of UCLC, FSPB_LS showed better consistency with the MC algorithm than observed in CLC. Notwithstanding, UCLC's OARs were highly sensitive to radiation dose and could result in potentially serious adverse reactions. Consequently, it is advisable to use the MC algorithm for dose calculation in both CLC and UCLC, while the application of FSPB_LS algorithm should be carefully considered.